- Email: [email protected]
HUMAN PLACENTAL LACTOGEN AND FETAL ABNORMALITY
1141 INFLUENZA AND VENTRICULAR SEPTAL DEFECT
with its initial introduction. The Collaborative Perinatal Project from N.I.N.D.S. has provided valuable data, but it cannot be expected to provide an answer to every question about environmental agents and birth defects. The hypothesised relationship between influenza and ventricular septal defect may or may not be correct, but we doubt that it is adequately tested in data from 1959-66. New York State Department of
Health,
DWIGHT T. JANERICH ANTHONY P. POLEDNAK.
HUMAN PLACENTAL LACTOGEN AND FETAL ABNORMALITY SIR,-Dr Gau and Dr Cadlereported 3 women who had abnormal fetuses whose human placental lactogen (H.P.L.) levels were persistently low. They suggest that this finding may act as a warning of an anomalous fetus. I have studied 30 H.P.L. samples taken from 13 mothers with anomalous fetuses between 26 and 39 weeks.2 The anomalies were: anencephaly (2), Down’s syndrome (2), congenital heart-disease (2) (Fallot’s tetralogy, transposition), atresia of the duodenum (1), diaphragmatic hernia (1),
omphalocele (1), meningocele (1), chondrodystrophia (1), Turner’s syndrome (1), and multiple anomalies (1). 9 fetuses died in utero or perinatally, but all the samples taken when the fetuses were still alive. The level of H.P.L. was generally low: 16 out of 30 samples were below my normal limit. This was, however, not associated with the fetal abnormality itself but rather with the pregnancy complication: pre-eclampsia (4), uterine bleeding (2), or class-D diabetes (1). In uncomplicated pregnancy, apart from fetal anomaly, the level of H.P.L. could be within normal limits. My impression is that the low H.P.L. level in itself only seldom warns against a fetal anomaly. This is further supported by the information that the fetus does not play any role in the synthesis or release of H.P.L. and the level of H.P.L. in fetal circulation is only about 1 % of maternal serum value.3
were
Department of Obstetrics and of Oulu, Oulu, Finland.
Gynæcology, University
OLAVI YLIKORKALA.
SCREENING FOR SPINA BIFIDA
SiR,-Dr Laurence’s article (Oct. 19, p. 939) is clear and informative. One of the procedures he discusses is the possible future use of measuring et-fetoprotein in maternal serum as a method of detecting a group of pregnant women, some of whom will have a child with spina bifida 1. 2. 3.
Gau, G., Cadle, G. Lancet, Sept. 28, 1974, p. 775. Ylikorkala, O. Acta obst. gynæc. scand. 1974, 53, suppl. 26. Grumbach, M. M., Kaplan, S. L., Sciarra, J. J., Burr, I. M. N.Y. Acad. Sci. 1968, 148, 501.
anencephaly.
proves reliable it could be
SiR,-Ms Rosenberg and Dr Heinonen’s analysis (Oct. 12, p. 903) of the seasonal occurrence of ventricular septal defect is not an adequate test of the specific hypothesis involving influenza. Dr Rothman and Dr Fyler (July 27, p. 193) hypothesised that influenza is the cause of their observed seasonal trend, and their data base covers a period which included the introduction of the A2 Hong Kong strain of influenza in 1968. Ms Rosenberg and Dr Heinonen tested the hypothesis by using birth data from 1959 to 1966. These data were gathered too late to show the major effect from the 1957 A2 Asian epidemic and too early to show an effect from the 1968 A2 Hong Kong epidemic. Although a new strain of influenza persists for several years, its most significant impact usually occurs
84 Holland Avenue, Albany, New York 12237, U.S.A.
Dr Laurence suggests that if this test performed as a routine during pregnancy, with the offer, to women with high levels, of amniocentesis followed by termination of pregnancy He says, should the amniotic ot-fetoprotein be high. rightly, that caution would have to be used in explaining a high serum level and the offer of amniocentesis to a woman without a previously affected child, and particularly if there were moral or religious objections to termination of
or
pregnancy.
I am worried by the suggestion that such a test to detect a fetal abnormality might become routine. I think that to explain a high level of serum-
SARAH BUNDEY.
PREDICTING RESPONSE OF HUMAN CANCER TO CHEMOTHERAPY SiR,—There are good reasons for doubting whether the response of a patient’s tumour to anti-cancer drugs can be predicted by assaying the effects of these drugs on tissue-cultures of the tumour, as conditions in vivo and in vitro differ profoundly in respects that greatly influence drug effectiveness.1,22 First, the proliferative kinetics and the extracellular environment of human tumour cells differ widely in the two conditions. Second, it is impossible for in-vitro experiments to reproduce the in-vivo disposal of a drug, which may involve activation and/or inactivation in the liver and other organs, and complex partitioning between various tissues. Third, cultures other than shortterm are likely to select clones of cells adapted to rapid growth in vitro, and these may be unrepresentative of the On the other hand, short-term tumour in the patient. cultures usually contain non-malignant cells also, and the conditions of assay generally make it impossible to distinguish between effects on normal and malignant cells. Accordingly, it is necessary to examine carefully claims, such as that of Holmes and Littlethat a good correlation is found between in-vitro and in-vivo drug responses. Holmes and Little claimed that both clinical and in-vitro responses were positive in 5 of their patients. However, 1 of these patients was given 4 drugs, and a mixture of all 4 was tested in tissue-culture, so that no conclusion can be drawn as to which of the drugs produced the clinical effect and which the in-vitro effect. In another 2 of these patients, 3 drugs were given, but only 1 or 2 of these were shown to be effective in vitro; the others were either ineffective or not tested. Clearly, the clinical responses 1. Lancet, 1972, i, 827. 2. Berenbaum, M. C.,
Sheard, C. E., Reittie, J. R., Bundick, J. Cancer, 1974, 30, 13. Holmes, H. L., Little, J. M. Lancet, Oct. 26, 1974, p. 985. Br.
Ann. 3.
R. V.
with its initial introduction. The Collaborative Perinatal Project from N.I.N.D.S. has provided valuable data, but it cannot be expected to provide an answer to every question about environmental agents and birth defects. The hypothesised relationship between influenza and ventricular septal defect may or may not be correct, but we doubt that it is adequately tested in data from 1959-66. New York State Department of
Health,
DWIGHT T. JANERICH ANTHONY P. POLEDNAK.
HUMAN PLACENTAL LACTOGEN AND FETAL ABNORMALITY SIR,-Dr Gau and Dr Cadlereported 3 women who had abnormal fetuses whose human placental lactogen (H.P.L.) levels were persistently low. They suggest that this finding may act as a warning of an anomalous fetus. I have studied 30 H.P.L. samples taken from 13 mothers with anomalous fetuses between 26 and 39 weeks.2 The anomalies were: anencephaly (2), Down’s syndrome (2), congenital heart-disease (2) (Fallot’s tetralogy, transposition), atresia of the duodenum (1), diaphragmatic hernia (1),
omphalocele (1), meningocele (1), chondrodystrophia (1), Turner’s syndrome (1), and multiple anomalies (1). 9 fetuses died in utero or perinatally, but all the samples taken when the fetuses were still alive. The level of H.P.L. was generally low: 16 out of 30 samples were below my normal limit. This was, however, not associated with the fetal abnormality itself but rather with the pregnancy complication: pre-eclampsia (4), uterine bleeding (2), or class-D diabetes (1). In uncomplicated pregnancy, apart from fetal anomaly, the level of H.P.L. could be within normal limits. My impression is that the low H.P.L. level in itself only seldom warns against a fetal anomaly. This is further supported by the information that the fetus does not play any role in the synthesis or release of H.P.L. and the level of H.P.L. in fetal circulation is only about 1 % of maternal serum value.3
were
Department of Obstetrics and of Oulu, Oulu, Finland.
Gynæcology, University
OLAVI YLIKORKALA.
SCREENING FOR SPINA BIFIDA
SiR,-Dr Laurence’s article (Oct. 19, p. 939) is clear and informative. One of the procedures he discusses is the possible future use of measuring et-fetoprotein in maternal serum as a method of detecting a group of pregnant women, some of whom will have a child with spina bifida 1. 2. 3.
Gau, G., Cadle, G. Lancet, Sept. 28, 1974, p. 775. Ylikorkala, O. Acta obst. gynæc. scand. 1974, 53, suppl. 26. Grumbach, M. M., Kaplan, S. L., Sciarra, J. J., Burr, I. M. N.Y. Acad. Sci. 1968, 148, 501.
anencephaly.
proves reliable it could be
SiR,-Ms Rosenberg and Dr Heinonen’s analysis (Oct. 12, p. 903) of the seasonal occurrence of ventricular septal defect is not an adequate test of the specific hypothesis involving influenza. Dr Rothman and Dr Fyler (July 27, p. 193) hypothesised that influenza is the cause of their observed seasonal trend, and their data base covers a period which included the introduction of the A2 Hong Kong strain of influenza in 1968. Ms Rosenberg and Dr Heinonen tested the hypothesis by using birth data from 1959 to 1966. These data were gathered too late to show the major effect from the 1957 A2 Asian epidemic and too early to show an effect from the 1968 A2 Hong Kong epidemic. Although a new strain of influenza persists for several years, its most significant impact usually occurs
84 Holland Avenue, Albany, New York 12237, U.S.A.
Dr Laurence suggests that if this test performed as a routine during pregnancy, with the offer, to women with high levels, of amniocentesis followed by termination of pregnancy He says, should the amniotic ot-fetoprotein be high. rightly, that caution would have to be used in explaining a high serum level and the offer of amniocentesis to a woman without a previously affected child, and particularly if there were moral or religious objections to termination of
or
pregnancy.
I am worried by the suggestion that such a test to detect a fetal abnormality might become routine. I think that to explain a high level of serum-
SARAH BUNDEY.
PREDICTING RESPONSE OF HUMAN CANCER TO CHEMOTHERAPY SiR,—There are good reasons for doubting whether the response of a patient’s tumour to anti-cancer drugs can be predicted by assaying the effects of these drugs on tissue-cultures of the tumour, as conditions in vivo and in vitro differ profoundly in respects that greatly influence drug effectiveness.1,22 First, the proliferative kinetics and the extracellular environment of human tumour cells differ widely in the two conditions. Second, it is impossible for in-vitro experiments to reproduce the in-vivo disposal of a drug, which may involve activation and/or inactivation in the liver and other organs, and complex partitioning between various tissues. Third, cultures other than shortterm are likely to select clones of cells adapted to rapid growth in vitro, and these may be unrepresentative of the On the other hand, short-term tumour in the patient. cultures usually contain non-malignant cells also, and the conditions of assay generally make it impossible to distinguish between effects on normal and malignant cells. Accordingly, it is necessary to examine carefully claims, such as that of Holmes and Littlethat a good correlation is found between in-vitro and in-vivo drug responses. Holmes and Little claimed that both clinical and in-vitro responses were positive in 5 of their patients. However, 1 of these patients was given 4 drugs, and a mixture of all 4 was tested in tissue-culture, so that no conclusion can be drawn as to which of the drugs produced the clinical effect and which the in-vitro effect. In another 2 of these patients, 3 drugs were given, but only 1 or 2 of these were shown to be effective in vitro; the others were either ineffective or not tested. Clearly, the clinical responses 1. Lancet, 1972, i, 827. 2. Berenbaum, M. C.,
Sheard, C. E., Reittie, J. R., Bundick, J. Cancer, 1974, 30, 13. Holmes, H. L., Little, J. M. Lancet, Oct. 26, 1974, p. 985. Br.
Ann. 3.
R. V.